Evaluation of biogenic amines in the faeces of children with and without autism by LC-MS/MS

Previous researchers have postulated that gastrointestinal bacteria may contribute to the development and maintenance of Autism Spectrum Disorders (ASD). There is evidence based on quantitative evaluation of the gastrointestinal bacterial population in ASD that this is unlikely and an alternate mechanism will be examined where the bacteria may contribute to the development of ASD via their metabolic products and the role of biogenic amines (BAs) will be investigated. In humans, BAs influence a number of physiological processes via their actions as neurotransmitters, local hormones and gastric acid secretion. Various amines have been implicated in several medical conditions such as schizophrenia and colon cancer. To date, the relationship between BAs and autism has not been explored. This study has been designed to identify differences (and/or similarities) in the level of Bas in faecal samples of autistic children (without gastrointestinal dysfunction: n = 14; with gastrointestinal dysfunction; n = 21) and their neurotypical siblings (n = 35) by LC-MS/MS. Regardless of the diagnosis, severity of ASD and gastrointestinal dysfunction there were no significant differences found between the groups. The findings suggest that BAs in the gastrointestinal tract do not play a role in the pathophysiology of gastrointestinal dysfunction associated with ASD.

The potential link between gut microbiota and IgE-mediated food allergy in early life

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field.

A novel model of sensitization and oral tolerance to peanut protein

The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.

A prospective analysis of pain experience, beliefs and attitudes, and pain management in a cohort of Danish surgical patients.

Background: 

Induced alkalosis and caffeine supplementation : effects on 2,000-m rowing performance

Introduction: The purpose of this investigation was to determine the effect of ingested caffeine, sodium bicarbonate, and their combination on 2,000-m rowing performance, as well as on induced alkalosis (blood and urine pH and blood bicarbonate concentration [HCO3 -]), blood lactate concentration ([La-]), gastrointestinal symptoms, and rating of perceived exertion (RPE). Methods: In a double-blind, crossover study, 8 well-trained rowers performed 2 baseline tests and 4 × 2,000-m rowing-ergometer tests after ingesting 6 mg/kg caffeine, 0.3 g/kg body mass (BM) sodium bicarbonate, both supplements combined, or a placebo. Capillary blood samples were collected at preingestion, pretest, and posttest time points. Pairwise comparisons were made between protocols, and differences were interpreted in relation to the likelihood of exceeding the smallest-worthwhile- change thresholds for each variable. A likelihood of >75% was considered a substantial change. Results: Caffeine supplementation elicited a substantial improvement in 2,000-m mean power, with mean (± SD) values of 354 ± 67 W vs. placebo with 346 ± 61 W. Pretest [HCO3 -] reached 29.2 ± 2.9 mmol/L with caffeine + bicarbonate and 29.1 ± 1.9 mmol/L with bicarbonate. There were substantial increases in pretest [HCO3 -] and pH and posttest urine pH after bicarbonate and caffeine + bicarbonate supplementation compared with placebo, but unclear performance effects. Conclusions: Rowers' performance in 2,000-m efforts can improve by ~2% with 6 mg/kg BM caffeine supplementation. When caffeine is combined with sodium bicarbonate, gastrointestinal symptoms may prevent performance enhancement, so further investigation of ingestion protocols that minimize side effects is required. ABSTRACT FROM AUTHOR

Effects of acute alkalosis and acidosis on performance

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed- model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athiete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly mod- erate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5mmoL/kg/BM (-0.3g/kgIBM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of l.SmmoL/kgIBM (-0.5gIkgJBM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5mmoL/kgIBM (-0.3glkg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (± 1 .1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ± 1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bi- carbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and am- monium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 glkg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. ABSTRACT FROM AUTHOR

The release and induced immune responses of a plant-made and delivered antigen in the mouse gut

This study investigated the site of release of a model vaccine antigen from plant cells and the corresponding induced immune response. Three plant tissues (leaf, fruit and hairy root) and two formulations (aqueous and lipid) were compared in two mouse trials. A developed technique that enabled detection of antigen release by plant cells determined that antigen release occurred at early sites of the gastrointestinal tract when delivered in leaf material and at later sites when delivered in hairy roots. Lipid formulations delayed antigen release from all plant materials tested. While encapsulation in the plant cell provided some protection of the antigen in the gastrointestinal tract and influenced antigen release, formulation medium was also an important consideration with regard to vaccine delivery and immunogenicity. Systemic immune responses induced from the orally delivered vaccine benefited from late release of antigen in the mouse gastrointestinal tract. The influences to the mucosal immune response induced by these vaccines were too complex to be determined by studies performed here with no clear trend regarding plant tissue site of release or formulation medium. Expression and delivery of the model antigen in plant material prepared in an aqueous formulation provided the optimal systemic and mucosal, antigen-specific immune responses.

Suicidal ideation and physical illness: Does the link lie with depression?

Objective
Medical illness is a risk factor for suicidality; however, disorder-specific risks are not well-known and these relationships are often explained by major depressive disorder (MDD). We aimed to investigate the relationship between suicidal ideation, MDD and medical illnesses in an age-stratified, population-based sample of men participating in the Geelong Osteoporosis Study.

Methods
Suicidal ideation and medical conditions were self-reported. Medical conditions were confirmed by medical records, medication use or clinical data where possible. MDD was determined using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition.

Results
Of the 907 men, 8.5% reported suicidal ideation. Thyroid disorders (OR 3.85, 95%CI 1.2–12.1), syncope and seizures (OR 1.96, 95%CI 1.1–3.5), liver disorders (OR 3.53, 95%CI 1.1–11.8; younger men only) and alcoholism (OR 2.15, 95%CI 1.1–4.4) were associated with increased odds of suicidal ideation, independent of age and MDD. Major vascular events doubled the odds of suicidal ideation but this was explained by MDD. No association was evident with high medical burden, musculoskeletal disease, metabolic factors, gastrointestinal disorders, headaches, cardiovascular disease, COPD, cancer and psoriasis.

Conclusion
Health care professionals should focus on identification, assessment and management of suicidal ideation in the medically ill in patients both with and without MDD.

Personality disorders and physical comorbidities in adults from the United States: data from the national epidemiologic survey on alcohol and related conditions.

There is a paucity of research examining the relationship between personality disorders (PDs) and chronic physical comorbidities. Consequently, we investigated associations between individual PDs and PD Clusters, and various common disease groups [cardiovascular disease (CVD), diabetes, arthritis and gastrointestinal disease (GI)] in a nationally representative survey of adults from the United States.

The role of sweet taste in satiation and satiety

Increased energy consumption, especially increased consumption of sweet energy-dense food, is thought to be one of the main contributors to the escalating rates in overweight individuals and obesity globally. The individual's ability to detect or sense sweetness in the oral cavity is thought to be one of many factors influencing food acceptance, and therefore, taste may play an essential role in modulating food acceptance and/or energy intake. Emerging evidence now suggests that the sweet taste signaling mechanisms identified in the oral cavity also operate in the gastrointestinal system and may influence the development of satiety. Understanding the individual differences in detecting sweetness in both the oral and gastrointestinal system towards both caloric sugar and high intensity sweetener and the functional role of the sweet taste system may be important in understanding the reasons for excess energy intake. This review will summarize evidence of possible associations between the sweet taste mechanisms within the oral cavity, gastrointestinal tract and the brain systems towards both caloric sugar and high intensity sweetener and sweet taste function, which may influence satiation, satiety and, perhaps, predisposition to being overweight and obesity.

Is fat the sixth taste primary? Evidence and implications

Taste is the chemical sense responsible for the detection of non-volatile chemicals in potential foods. For fat to be considered as one of the taste primaries in humans, certain criteria must be met including: class of affective stimuli; receptors specific for the class of stimuli on taste bud cells (TBC); afferent fibers from TBC to taste processing regions of the brain; perception independent of other taste qualities; and downstream physiological effects. The breakdown products of the macronutrients carbohydrates (sugars) and protein (amino acids) are responsible for activation of sweet and umami tastes respectively. Following the same logic the breakdown products of fat being fatty acids are the likely class of stimuli for fat taste. Indeed, psychophysical studies have confirmed fatty acids of varying chain length and saturation are orally detectable by humans. The most likely fatty acid receptor candidates located on TBC are CD36, G protein-coupled receptor 120. Once the receptors are activated by fatty acids a series of transduction events occurs causing the release of neurotransmitters towards afferent fibers signalling the brain. Whether fatty acids elicit any direct perception independent of other taste qualities is still open to debate with only poorly defined perceptions for fatty acids reported. Others suggest that the fatty acid taste component is at detection threshold only and any perceptions are associated with either aroma or chemesthesis. It has also been established that oral exposure to fat via sham feeding stimulates increases blood triacylglycerol concentrations in humans. Therefore, overall, with the exception of an independent perception, there is consistent emerging evidence that fat is the sixth taste primary. The implications of fatty acid taste go further into health and obesity research with the gustatory detection of fats and their contributions to energy and fat intake receiving increasing attention. There appears to be a coordinated bodily response to fatty acids throughout the alimentary canal; those who are insensitive orally are also insensitive in the gastrointestinal tract and overconsume fatty food and energy. The likely mechanism linking fatty acid taste insensitivity with overweight and obesity is development of satiety after consumption of fatty foods.

Malnutrition: significance, prevalence and management of the hospitalised surgery patient

Malnutrition is prevalent and poorly diagnosed in hospitalised patients, with high rates of malnutrition seen in surgical patients. The administration of a specialised immuno-nutrition supplement is beneficial for malnourished patients undergoing gastrointestinal surgery, and a multidisciplinary team approach improves nutritional care for patients.

A systematic review of adherence to restricted diets in people with functional bowel disorders

Functional bowel disorders such as irritable bowel syndrome are commonly experienced within the population, and have an adverse impact on emotions, physical well-being, social activity, and occupational output. Adherence to a restricted diet can reduce symptoms, which in turn leads to increased quality of life and well-being. The aim of this review was to assess the extent to which predictors of dietary adherence have been considered in studies relating to functional bowel disorders and following a restricted diet. This was done firstly by examining such studies which contained a measure or indicator of adherence, and then by examining predictors of adherence within and between studies. A search of PsycINFO, Medline, CINAHL, Web of Science, and Cochrane databases was performed during July 2014, with the search criteria including relevant terms such as gastrointestinal disorder, irritable bowel syndrome, diet, and adherence. Of an initial 7927 papers, 39 were suitable for inclusion. Fourteen of the 39 studies included had a structured measure or indicator of dietary adherence, and the remaining 25 mentioned adherence without any structured levels of adherence. There was little investigation into the predictors of adherence, with symptom relief or induction being the primary goal of most of the studies. This review indicates that predictors of dietary adherence are rarely considered in research regarding functional bowel disorders. Further investigation is needed into the variables which contribute to rates of adherence to restricted diets, and more rigorous research is needed to characterise those individuals most likely to be non-adherent. Such research is necessary to ensure that people with these conditions can be provided with appropriate support and interventions.

Maternal creatine homeostasis is altered during gestation in the spiny mouse: is this a metabolic adaptation to pregnancy?

BACKGROUND: Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. METHODS: Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. RESULTS: Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term. CONCLUSION: Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.

Differences in hormone localisation patterns of K and L type enteroendocrine cells in the mouse and pig small intestine and colon

 This study has investigated the patterns of colocalisation of the conventional K cell marker, glucagon-like insulinotropic peptide (GIP), and the L cell markers, glucagon like peptide-1 (GLP-1) and peptide YY (PYY), in enteroendocrine cells (EEC) of the small intestine and colon of mouse and pig. All combinations of the hormones, 3 in a cell, 2 in a cell and 1 at a time, were encountered. In both species, the three most common EEC types contained (1) both GLP-1 and PYY but not GIP, (2) GLP-1 alone or (3) GIP plus GLP-1 without PYY. Few GIP plus PYY cells and rare cells containing all 3 hormones were encountered. Gradients of cell types occurred along the intestine. For example, in mouse, there were no PYY cells in the duodenum and few in the jejunum, but >50 % of labelled EEC in the distal ileum and colon were PYY immunoreactive. By contrast, over 40 % of EEC in the pig duodenum contained PYY, and most also contained either GLP-1 or GIP. The gradient in pig was less pronounced. It is concluded that the traditional classification of K and L cells requires revision, and that there are major inter-species differences in the patterns of colocalisation of hormones that have been used to characterise K and L cells.